Int. J. Environ. Res. Public Health 2011, 8, 861-874; doi:10.3390/ijerph8030861
OPEN ACCESS
International Journal of
Environmental Research and
Public Health
ISSN 1660-4601
www.mdpi.com/journal/ijerph
Article
Long-Term Low-Level Arsenic Exposure Is Associated
with Poorer Neuropsychological Functioning: A Project
FRONTIER Study
Sid E. O’Bryant 1,2,*, Melissa Edwards 3, Chloe V. Menon3, Gordon Gong 1 and Robert Barber 4
1
2
3
4
F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Sciences
Center, 3601 4th St., STOP 6323, Lubbock, TX 79430, USA; E-Mail: [email protected]
Department of Neurology, Texas Tech University Health Sciences Center, 3601 4th St., STOP
8321, Lubbock, TX 79430, USA
Department of Psychology, Texas Tech University, 2500 Broadway, STOP 2051, Lubbock,
TX 79409, USA; E-Mails: [email protected] (M.E.); [email protected] (C.V.M.)
Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer’s Disease,
University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Ft Worth,
TX 76107, USA; E-Mail: [email protected]
* Author to whom correspondence should be addressed; E-Mail: [email protected];
Tel.: +1-806-743-1338; Fax: +1-806-743-4510.
Received: 10 February 2011; in revised form: 2 March 2011 / Accepted: 9 March 2011 /
Published: 15 March 2011
Abstract: Exposure to elements in groundwater (toxic or beneficial) is commonplace yet,
outside of lead and mercury, little research has examined the impact of many commonly
occurring environmental exposures on mental abilities during the aging process. Inorganic
arsenic is a known neurotoxin that has both neurodevelopmental and neurocognitive
consequences. The aim of this study was to examine the potential association between
current and long-term arsenic exposure and detailed neuropsychological functioning in a
sample of rural-dwelling adults and elders. Data were analyzed from 434 participants
(133 men and 301 women) of Project FRONTIER, a community-based participatory
research study of the epidemiology of health issues of rural-dwelling adults and elders. The
results of the study showed that GIS-based groundwater arsenic exposure (current and
long-term) was significantly related to poorer scores in language, visuospatial skills, and
executive functioning. Additionally, long-term low-level exposure to arsenic was
Int. J. Environ. Res. Public Health 2011, 8
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significantly correlated to poorer scores in global cognition, processing speed and
immediate memory. The finding of a correlation between arsenic and the domains of
executive functioning and memory is of critical importance as these are cognitive domains
that reflect the earliest manifestations of Alzheimer’s disease. Additional work is
warranted given the population health implications associated with long-term low-level
arsenic exposure.
Keywords: arsenic; chronic exposure; environmental exposure; cognition; rural health
1. Introduction
The detrimental impact of acute high-level exposure to arsenic on health is well established;
however, prior work has also documented adverse consequences of prolonged exposure to
groundwater arsenic at levels below the current U.S. standard of 10 μg/L. Chronic exposure to
low-levels of arsenic through drinking water is common in the U.S. where 13.6% of sampled public
water-supply systems exceeded 5 μg/L and 25% exceeded 2 μg/L [1]. Such exposure has been found to
increase risk for a range of diseases including hypertension, diabetes, coronary artery disease, skin
melanosis, cancer, and poorer cognition [2-8]. Therefore, over 40 million Americans are at an
increased risk for negative health consequences resulting from being exposed to low-levels of arsenic
over the course of their lifetime [1]. In fact, it has been proposed that exposure to environmental toxins,
including arsenic, has caused a ―silent pandemic‖ in modern society that has gone undetected [9]. This
circumstance has likely remained unnoticed because the neurodevelopmental and neurotoxic
consequences of in utero exposure (along with chronic lifetime exposure) may not become evident
until neuronal attrition associated with aging occurs [9]. To date, however, no prior work has been
published looking at the potential impact of long-term low-level arsenic exposure on cognitive
functioning among adults and elders. The purpose of this study was to take a first-step towards
addressing this gap in the public health literature.
There is ample reason to hypothesize an association between chronic arsenic exposure at low levels
and neuropsychological dysfunction. Inorganic arsenic at high doses is a known neurotoxin with
both neurodevelopmental and neurocognitive consequences. From a neuropathological standpoint,
arsenic exposure has been associated with an increase in the production of β amyloid [10],
hyperphosphorylation of tau protein [11], oxidative stress [12], inflammation [13,14], endothelial cell
dysfunction [15] and angiogenesis [16], all of which have been linked to cognitive dysfunction and are
proposed mechanisms underlying Alzheimer’s disease [3,17-19]. In animal models, arsenic exposure
has been shown to cause morphologic and neurochemical alterations in the hippocampus and other
memory-related neuronal structures and expected learning and memory deficits have been
noted [15,20,21]. However, the direct link between chronic low-level arsenic exposure and detailed
neuropsychological status remains untested.
Despite the National Research Council’s call for epidemiological studies of the non-cancer health
consequences of long-term low-level arsenic exposure [7,8], little research has been conducted to date.
This is not for lack of interest; however, the methods for conducting such investigations have yet to be
Int. J. Environ. Res. Public Health 2011, 8
863
established. The ideal situation is one where a biomarker of chronic exposure is available, which is the
case when considering lead. Bone lead level measurement via K-shell-x-ray fluorescence has been
used as a biomarker of long-term exposure [22] and the correlation between such exposure and
cognitive functioning has been studied [23,24]. However, a valid biomarker for long-term arsenic
exposure is lacking. One method that has been utilized is to reconstruct chronic exposures according to
retrospective report of the level as well as the duration of exposure. In the PHYTHONER study, Baldi
and colleagues [25] have documented a detrimental impact of long-term pesticide exposures on
neurocognitive functioning among French vineyard workers using this approach. In countries where
high levels of arsenic exposure have been documented for decades (e.g., areas of China, Bangladesh,
and Mexico), researchers have historical data regarding exposure levels that can be utilized to create
models of chronic exposure. In the U.S., the state of Texas offers a very unique situation given that the
Texas Water Development Board (TWDB) has been monitoring well-water levels of a large number of
chemicals including arsenic, for over 15 years across the state. Additionally, we have been conducting
an epidemiological study of rural health, Project FRONTIER, for several years in two West Texas
counties with mean groundwater arsenic levels that are below the U.S. standard. As part of this
protocol, we have collected subjects’ (1) exact residential location and (2) number of years living at
that location. Therefore, combining data from the TWDB and Project FRONTIER can create estimates
of current and long-term arsenic exposure. Groundwater arsenic concentration at each subject’s home
can be estimated with Geographic Information System (GIS) approach (the ArcGIS program) based on
the residential location’s distances to surrounding wells with known groundwater arsenic
concentrations provided by TWDB. The purpose of the current study was to examine the potential
association between current and long-term arsenic exposure estimated by the GIS methods and detailed
neuropsychological functioning in a sample of rural-dwelling adults and elders. Based on our prior
work, as well as work with children and adolescents, we hypothesized that increased low-level arsenic
exposure would be significantly correlated with poorer scores in the domains of global cognition,
executive functioning, memory, and language.
2. Experimental Section
2.1. Participants
Data from 434 participants (133 men and 301 women) from Project FRONTIER were analyzed.
Project FRONTIER is an ongoing epidemiological study of cognitive aging among rural-dwelling
individuals. Project FRONTIER utilizes a community-based participatory research (CBPR) approach,
which is a research methodology that involves partnering communities with scientific groups to
conduct studies of human disease that is growing rapidly in terms of use and acceptance in the
scientific community. CBPR is particularly useful when working with underserved communities that
may not respond to classic approaches (e.g., random digit dialing, mail surveys) and is very well suited
to rural health research; CBPR is supported by and recommended for rural research by the National
Institute of Environmental Health Sciences [26]. In Project FRONTIER, we have spent several years
establishing and maintaining our community ties through local advisory boards, presentations, hiring
of local workers into the research infrastructure, and partnering with community entities for
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864
completion of parts of the research protocol (i.e., blood work and medical examinations); our CBPR
process for maintaining this translational research platform has been described in detail elsewhere [27].
Briefly, we partner with the local hospitals and clinics (who conduct the medical examinations and
clinical labs as well as provide office space) as well as the senior citizen’s organizations. Our
community recruiters, community individuals, and research staff present information about the study at
community events as well as through door-to-door solicitation. The distribution of participants
recruited into the study (Cochran Cohort & Parmer Cohort) as compared to all eligible individuals by
county (Cochran County & Parmer County) by race/ethnicity, age, education, and gender are provided
below in Figure 1. As can be seen from these figures, the demographic composition of our cohort
closely resembles that of the eligible population from which they are drawn.
Figure 1. Demographic comparison of enrolled participants (Cochran Cohort & Parmer
Cohort) versus all eligible individuals in each county (Cochran County & Parmer County)
for race/ethnicity, age, education, and gender.
2.2. Procedures
The protocol includes a standardized medical examination, clinical labs and neuropsychological
testing, as well as an interview with the participant and a brief interview with an informant. Inclusion
criteria are (1) age 40 and above and (2) residing in one of the counties participating in Project
FRONTIER. The two counties currently part of project FRONTIER are Cochran County and Parmer
County, both located west of Lubbock, Texas, on the Texas—New Mexico border. The U.S. Census
conducted in 2008 indicated that the Cochran County comprised 3,501 residents with 1,609 individuals
age 40 and over (779 men and 830 women), compared to 9,639 residents for Parmer County including
3,937 individuals age 40 and over (1,906 men and 2,031 women). Additionally, twenty-two percent of
Int. J. Environ. Res. Public Health 2011, 8
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Cochran County inhabitants were reported to live below the poverty level, relative to 14% reported in
Parmer County. The principal economic land use in Cochran and Parmer County is large-scale
irrigated farming (cotton and wheat), ranching, and oil and natural gas production. Participant
recruitment is conducted by community recruiters through different means including brochures/flyers,
presentations and events, as well as, in-person and/or door-to-door solicitation. All participants signed
written informed consent and Project FRONTIER is conducted under an IRB approved protocol.
The neuropsychological test battery was comprised of instruments covering a range of cognitive
domains. The Mini-Mental State Examination (MMSE) [28] is the most commonly administered
psychometric screening assessment of global cognitive functioning. Since its development, there has
been a wealth of literature published on the MMSE demonstrating it to be a relatively sensitive marker
of dementia [29]. The Exit Interview (EXIT25) [30] is a well-validated global measure of executive
control that covers a range of tasks including sequencing, fluency, anomalous sentence repetition,
thematic perception, automatic behaviors, go-no-go and automatic behavior, among others. EXIT25
scores are significantly correlated with other validated measures of executive functioning [30]. Scores
range from zero to 50 with higher scores suggestive of greater impairment; a score of 15 or greater best
discriminates non-demented elderly controls from those with dementing illnesses. The Repeatable
Battery for the Assessment of Neuropsychological Status (RBANS) [31] is a brief neuropsychological
instrument that assesses multiple cognitive domains [32]. It contains 12 subtests that combine to create
five indices: Attention, Language, Visuospatial/Constructional abilities, as well as Immediate and
Delayed recall. The RBANS has accumulated a large amount of normative data [33] and has well
established psychometric properties [34]. The Trails Making Test (TMTA and TMTB), is a
neuropsychological instrument that measures attention, processing speed and mental flexibility, and is
considered to be a sensitive marker of cognitive dysfunction and decline [35]. The Controlled Oral
Word Association Test (COWAT) [35] assesses both phonemic (FAS) and categorical (Animal
Naming) verbal fluency, both of which are standard neuropsychological assessment techniques with
high sensitivity to cognitive dysfunction and dementia [35].
Determination of GIS-Arsenic. Geographic information system (GIS) is a way of displaying and
analyzing geographically referenced information. GIS-based methods are commonly used to estimate
environmental exposures [3,36-39]. We used the Environmental Systems Research Institute [40]
ArcGIS (release 9.2) program to plot a point for each of the 16,335 arsenic ground water
measurements that are readily available from the Texas Water Development Board (TWDB) [41].
Through inverse distance weighted (IDW) interpolation, the ArcGIS software builds a three
dimensional surface map from a list of points. Each point’s influence is weighted based off its distance
to that section of the map, which was generated using 12 well measurements from the TWDB within
the immediate geographic vicinity. Each of the study participant’s current residential address was
geocoded with the ArcGIS StreetMap data. Finally, GIS-arsenic concentration was calculated by
extracting the estimated arsenic value from the IDW surface at each resident’s location. The maps of
arsenic concentration in Texas (left) and Texas Panhandle (right) are presented below (Figure 2).
Arsenic groundwater levels are found to increase from Parmer County (15-year mean As level of
3.0 μg/L) south to Cochran County (15-year mean As value of 7.4 μg/L with a maximum of 15.6 μg/L
at the ―hot spot‖). Additionally, the length of residential history of residents from our pilot study
suggests that large portions of the community are long-term residents averaging over 30 years living in
Int. J. Environ. Res. Public Health 2011, 8
866
their respective communities. Combined, these data demonstrate that the two counties selected for this
study provide an optimal naturalistic setting to investigate long-term low-level arsenic exposure
from groundwater.
Figure 2. Ground water arsenic measurements form the Texas Water Development Board (TWDB).
Calculation of long-term low-level arsenic exposure. In order to estimate long-term low-level
arsenic exposure, we used readily available TWDB historical data and data from Project FRONTIER
regarding current residential address as well as years living at that residence. We examined 15-years of
TWDB water arsenic levels from wells within the communities of Project FRONTIER. We estimated
long-term low-level exposure by multiplying current estimated arsenic levels by the number of years
residing in current home. Similar methods for estimating long-term exposure have been utilized
previously [42,43]. As part of a different research study, we pilot tested the comparability between
observed and estimated (current) groundwater arsenic levels. We collected data from 7 rural wells and
examined their actual values by an atomic fluorescence method [42,43] and compared these data with
their respective GIS-estimated arsenic concentrations. GIS-estimated versus measured values are listed
in Table 1. GIS-estimated arsenic concentrations were quite close to measured values except wells
number 6 and 7, of which GIS-arsenic values are 4.6 and 4.2 μg/L higher than the measured values.
However, the ranks of the two series of value are nearly identical (with the exception that rank 6 and 7
based GIS approach for well #6 and #7 are a tie by measured values).
Linear regression models were created with SPSS version 18 using raw neuropsychological test
scores as outcome variables and either current or long-term arsenic exposure estimates as predictor
variables. Covariates considered in the models included age, gender, education, ethnicity, language of
administration, and APOE4 status (present/absent). Given that selenium is known to impact arsenic
toxicity, current groundwater selenium estimates were also calculated via GIS methods and were
entered into the models as a covariate. We utilized receiver operating characteristic (ROC) curves to
estimate the accuracy of arsenic levels in classifying cognitive status (impairment versus no
Int. J. Environ. Res. Public Health 2011, 8
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impairment) by reviewing the area under the ROC curve (AUC). Statistical significance was set at
p < 0.05.
Table 1. Comparison of GIS-estimated vs. measured arsenic concentration in seven wells (μg/L).
Well #
GIS-Estimated
Measured
1
2
3
4
5
6
7
12.9
12.0
11.6
10.5
7.0
6.2
5.8
14.2
14.4
13.3
10.7
5.8
1.6
1.6
3. Results and Discussions
The mean age and education of the 434 participants was 62.12 (sd = 12.81; range = 40–96) and
10.84 (sd = 4.46; range = 0–20), respectively. Seventy-nine percent (n = 344) of the sample was tested in
English, with the remainder completing the assessment in Spanish. Ninety-seven percent of the sample
self-reported their racial status as White and 42% (n = 180) reported their ethnicity as Hispanic, with the
majority (n = 171) being of Mexican American origin. Of those participants genotyped (n = 440),
329 (75%) were APOE4 negative and 111 (25%) were APOE4 positive. Demographic characteristics of
the sample are presented in Table 2. Estimated mean current arsenic level was 6.33 μg/L (sd = 3.03,
range = 2.19–15.26). The 15-year mean arsenic concentrations in Parmer and Cochran County, TX were
3.06 μg/L and 7.39 μg/L, respectively. In both counties, there was less than 2 μg/L variability over any
given time period with results remaining very stable over this time period. There were 301 participants
with all requisite data for calculation of long-term arsenic exposure at current household; mean long-term
exposure was 240.15 μg/L-years (sd = 182.96; range = 2.87–972.83). On average, participants resided in
their current residence for 34.12 years (sd = 20.01years, range = 1–80 years).
Table 2. Demographic characteristics.
Age
Education
MMSE
Arsenic (μg/L)
Long-Term Arsenic (μg/L-years)
FAS Total
Animal Naming
TMTA (seconds)
TMTB (seconds)
RBANS Immediate Memory
Mean (sd)
62.12(12.8)
10.84 (4.46)
27.54 (2.80)
6.33 (3.03)
240.15 (182.96)
27.93 (12.62)
16.35 (5.01)
56.73 (34.00)
127.32 (77.67)
41.11 (9.39)
Range
40–96
0–20
12–30
2.19–15.26
2.87–972.83
0–71
0–32
18–420
33–532
5–61
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868
Table 2. Cont.
Mean (sd)
RBANS Visuospatial
28.80 (6.26)
RBANS Language
27.36 (5.46)
RBANS Attention
45.51 (16.72)
RBANS Delayed Memory
35.76 (9.25)
EXIT-Total
7.31 (4.77)
Note: RBANS scores are reflective of raw index scores.
Range
0–40
8–42
9–100
10–60
0–23
Current estimated groundwater arsenic exposure level was significantly associated with poorer
scores in language (RBANS Language scores, B(SE) = −0.458 (0.171), p = 0.008), visuospatial skills
(CLOX2, B(SE) = −0.118 (0.060), p = 0.048), and executive functioning (CLOX 1 B(SE) = −0.225
(0.080), p = 0.005) (see Table 3). Current arsenic exposure significantly classified cognitive
dysfunction (AUC = 0.58, 95% CI = 0.51–0.65, p = 0.03).
Table 3. Arsenic levels impact on neuropsychological functioning.
Long-Term Arsenic
Current Arsenic
B (SE)
p-value
B (SE)
p-value
MMSE
−0.003 (0.001)
0.004
−0.116 (0.088)
0.191
CLOX 1
−0.001 (0.001)
0.290
−0.225 (0.080)
0.005
CLOX 2
−0.001 (0.001)
0.038
−0.118 (0.060)
0.048
FAS
−0.012 (0.004)
0.002
−0.724 (0.377)
0.056
Animal Naming
−0.002 (0.002)
0.250
−0.138 (0.181)
0.446
TMTA
0.034 (0.014)
0.016
0.986 (1.17)
0.400
TMTB
0.037 (0.029)
0.209
4.23 (2.44)
0.084
RBANS Immediate Memory
−0.010 (0.003)
0.003
0.187 (0.311)
0.547
RBANS Visuospatial
−0.001 (0.002)
0.543
−0.342 (0.211)
0.106
RBANS Language
−0.005 (0.002)
0.017
−0.458 (0.171)
0.008
RBANS Attention
−0.007 (0.005)
0.118
−0.466 (0.423)
0.271
RBANS Delayed Memory
0.001 (0.003)
0.651
0.537 (0.303)
0.077
EXIT Total
0.006 (0.002)
0.000
0.475 (0.139)
0.077
Note: Covariates included age, gender, education, language of administration (English or Spanish),
selenium level and APOE4 presence (yes/no); B = unstandardized regression coefficient;
SE = standard error.
Long-term low-level exposure to arsenic was significantly associated with poorer scores in global
cognition (MMSE B(SE) = −0.003 (0.001), p = 0.004), visuospatial skills (CLOX 2 B(SE) = −0.001
(0.001), p = 0.038), language (FAS B(SE) = −0.012 (0.004), p = 0.002; RBANS Language
B(SE) = −0.005 (0.002), p = 0.017), processing speed (TMTA B(SE) = 0.034 (0.014), p = 0.016),
executive functioning (EXIT B(SE) = 0.006 (0.002), p < 0.001), and immediate memory (RBANS
Immediate Memory B(SE) = −0.010 (0.003), p = 0.003). Long-term low-level arsenic exposure
significantly classified cognitive impairment (AUC = 0 .62, 95% CI = 0.55–0.69, p = 0.001).
With the rapidly growing number of elders world-wide, there is a great need for research examining
factors that impact cognition among adults and elders. Prior work has consistently demonstrated the
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adverse health consequences of high levels of arsenic exposure. As a result, the U.S. acceptable
standard of arsenic concentration was reduced in 2001 from 50 μg/L to 10 μg/L. However, as pointed
out by the National Research Council, there remains a need for research examining the non-cancer
health effects of low-level arsenic exposure [7,8] using longitudinal methodologies. Our current
findings suggest that long-term low-level arsenic exposure is detrimental for the cognitive status of
adults and elders. Our findings are consistent with prior work linking environmental exposure to
arsenic to poorer neuropsychological functioning. Bolla-Wilson and Bleeker [44] evaluated the
neurocognitive functioning of a 50-year-old adult following acute exposure to arsenic and documented
deficits in learning and memory, which improved over time with no subsequent exposures. Similarly,
Wright and colleagues [45] examined the neuropsychological profile of 31 school-aged children
residing in Ottawa County, Oklahoma, which contains the Tar Creek Superfund site, and found higher
hair arsenic levels to be significantly associated with poorer scores on tests of intelligence and memory.
Tsai and colleagues [46] evaluated 49 junior school students and found that higher chronic
groundwater arsenic exposure was significantly related to poorer memory and executive functioning
(i.e., switching attention). In a sample of 602 school children age 6–8 years, Rosado and colleagues [47]
found that higher urinary arsenic levels were significantly associated with poorer visuospatial skills,
intelligence, attention and executive functioning. In our study, higher levels of current groundwater
arsenic exposure (though still low-level exposure) was related to poorer visuospatial skills, language,
and executive functioning. Increased levels of long-term low-level exposure were related to
significantly poorer performance in the domains of global cognition, language, executive functioning,
as well as memory. The current study is, however, different from all of the previously conducted work
in several ways. First, the mean and median values of groundwater exposures in the communities
evaluated in this study are below the current U.S. acceptable standard and are therefore reflective of
low-level exposure. Second, we examined the impact of exposure on neuropsychological functioning
in a community-based sample of rural-dwelling adults and elders rather than school children. Lastly,
ours is the first to study the impact of estimated long-term low-level arsenic exposure on detailed
neuropsychological functioning. Our results are consistent with and extend prior work to adults and
elders exposed at lower levels of groundwater arsenic [3].
The consistent finding of arsenic being related to the domains of executive functioning and memory
is of critical importance as these are cognitive domains that may change as part of the normal aging
process and may even be the earliest manifestations of Alzheimer’s disease [48,49]. This is particularly
important for the long-term estimates, which as can be seen from Table 3, are more strongly related
with cognitive status. Therefore, it is possible that the impact of low-level arsenic exposure on
neuropsychological functioning happens over time, which fits with the developmental course of
Alzheimer’s disease. Alzheimer’s disease is a disease of insidious onset with slow progression that
begins decades before clinical manifestation. While it has been suggested that research should focus on
preventative strategies for Alzheimer’s disease [50], the recent NIH consensus panel suggested that
there are no preventative strategies currently available for Alzheimer’s disease, albeit dietary factors
were suggested as having promise. The notion of groundwater exposure to arsenic as a risk factor for
late-life Alzheimer’s disease offers potential for the first ever population-wide preventative effort
aimed at preventing and/or delaying onset of this disease, which could be accomplished by revision of
the Safe Drinking Water Act (SDWA).
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There are limitations to the current study. One limitation is the cross-sectional nature of the data,
which does not allow for inference of causality. Longitudinal assessment of this topic will be
conducted through Project FRONTIER as follow-up waves are completed. The key limitation to the
current study is the lack of either a biomarker of arsenic exposure (i.e., blood, hair, or nail levels) or
direct measurement of the actual water arsenic levels at participant homes. However, the existence of
the TWDB data provides an exceptional opportunity to model chronic arsenic exposure and the state
can serve as a naturalistic setting for future studies. This is due to the fact that there are several ―hot
beds‖ of high arsenic levels across the state, even though the majority of the state is well below the
current EPA standard. It is shown that GIS-estimated arsenic concentrations are very close to the
measured values, particularly in terms of rank. Future Project FRONTIER studies will examine serum
arsenic levels along with current household water levels. We cannot at this point conclude that longterm low-level arsenic consumption through water is causally related to poorer cognition from the
current data. However, we can assert that those individuals who have resided for long periods of time
in regions that have historically low levels of arsenic in groundwater supplies are at increased risk for
cognitive dysfunction. This finding is certainly novel and warrants further investigation.
4. Conclusions
Our findings suggest an association between low-level arsenic exposure and neuropsychological
functioning, as originally hypothesized. Of particular interest is the association between long-term
low-level arsenic exposure and neuropsychological functioning across a broader range of domains than
current exposure. Our findings offer the first direct evidence that low level arsenic exposure,
extrapolated from current arsenic levels and self report of duration in residence is associated with
poorer neuropsychological functioning among community-dwelling adults and elders in the U.S.
Further research is needed to investigate this topic and, if cross-validated, this research will provide
ample justification for a re-evaluation of current policy related to acceptable groundwater
arsenic levels.
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